Table 1.
Key Synaptic Phenotypes in Mouse Models of Diseased Cognition
| Disease Model | LTP | LTD | Inhibition | Connectivity |
|---|---|---|---|---|
| Neurodevelopmental | ||||
| Angelman synd. | Decreased [40,46] | Decreased [47] | ||
| Ube3A KO | ||||
| Down synd. | Decreased [48-50] | Increased [51] | Increased [24,49] | Decreased/Increased* [24,52,53] |
| Trisomy | ||||
| Fragile × synd. | Decreased/Increased [54-56] | Increased [57] | Decreased [58-60] | Decreased/Increased* [25,27,28] |
| Fmr1 KO | ||||
| FRAXE synd. | Increased [61] | |||
| Fmr2 KO | ||||
| Neurofibromat. | Decreased [62-64] | Increased [62,63] | ||
| Nf1 het | ||||
| Rett synd. | Decreased [65,66] | Decreased [65] | Increased [67] | Decreased [68,69] |
| Mecp2 KO | ||||
| Tuberous Scler. | Decreased [70] | Decreased [70] | Decreased [71,72] | |
| Tsc1 KO | ||||
| Tsc2 KO (rat) | ||||
| Various XLMR | Decreased [73,74] | Decreased [75] | ||
| Ophn1 KO | ||||
| Pak3 KO | ||||
| Gdi1 KO | ||||
| Neuropsychiatric | ||||
| Schizophrenia | Decreased [76,77] | Decreased [78] | Decreased [78] | Decreased [76,79-81] |
| Disc1 mut | ||||
| Reelin het | ||||
| 22q11 del | ||||
| Neurodegenerative | ||||
| ALS | Increased [82] | Decreased [83] | ||
| Sod1 mut | ||||
| Alzheimer's | Decreased [30,32,84-86] | Increased [30,32] | Decreased/Increased* [26,84,87-89] | |
| App mut | ||||
| Ps1/Ps2 KO | ||||
| App/Ps1 mut | ||||
| Huntington's | Decreased [38,90,91] | Decreased/Increased [92,93] | ||
| Htt mut | ||||
| Parkinson's. | Decreased/Increased [94,95] | Decreased [94] | ||
| Dj-1 KO | ||||
| Parkin KO | ||||
| SCA | Decreased [96,97] | Decreased [98] | ||
| Sca1 mut | ||||
| Fgf14 KO | ||||
The first column lists neurological conditions associated with impaired cognition, along with corresponding diseased-linked mutations that have been modeled in mice. The remaining columns list reported alterations to LTP, LTD, synaptic inhibition, and connectivity in each group of mouse models. Asterisks indicate reports of increased connectivity that are accompanied by concomitant decreases in connectivity in different neuronal subpopulations. As well as direct physiological measurement of synaptic connectivity, indirect findings of altered dendritic spine density or axonal projections were considered indications of altered connectivity. While the connections within CA3 are the primary focus of our simulations, studies of synapses throughout the hippocampus are listed to allow a comprehensive comparison of existing data. When no hippocampal data was available, studies of other cortical neuron populations were included.